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Cardiovascular Research Advance Access originally published online on May 2, 2008
Cardiovascular Research 2008 79(1):161-168; doi:10.1093/cvr/cvn111
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries

Akiko Hirao1, Kazunao Kondo2, Kazuhiko Takeuchi1, Naoki Inui1, Kazuo Umemura2, Kyoichi Ohashi3 and Hiroshi Watanabe1,*

1 Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
2 Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
3 Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan

* Corresponding author. Tel: +81 53 435 2385; fax: +81 53 435 2384. E-mail address: hwat{at}hama-med.ac.jp

Aims: Denudation and regeneration of the vascular endothelium are important in the pathogenesis of atherosclerosis. The aim of this study is to clarify the mechanisms of functional alterations in remodelled arteries following endothelial injury.

Methods and results: Non-mechanical endothelial injury was induced by 540-nm light irradiation of rose Bengal in femoral arteries of Wistar rats. Endothelium-dependent vasodilation was assessed by the response to acetylcholine (ACh) 1, 2, and 4 weeks after the injury. In control arteries, ACh-induced relaxation was mainly nitric oxide-dependent at all study time points. In injured arteries, this response was completely restored at 1 week, but was more dependent on KCl-sensitive endothelium-derived hyperpolarizing factor production during the first 2 weeks. Cyclooxygenase (COX) isoforms 1 and 2 were detected in the endothelium of injured arteries, and inhibition of prostanoids production with the non-specific COX inhibitor indomethacin substantially enhanced the ACh-induced vasorelaxation response in injured arteries, but did not affect control arteries. Similar effects were observed with the COX-1 inhibitor SC-560, the COX-2 inhibitor NS-398, the thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist SQ29548 and the PGF2{alpha} receptor antagonist AL-8810. However, the TX synthetase inhibitor OKY-046 had no effect on ACh-induced relaxation in injured arteries.

Conclusion: In remodelled arteries following photochemical endothelial injury, the vasoconstrictive prostanoids PGH2 and PGF2{alpha}, but not TXA2, contribute to changes in endothelium-dependent vascular response via COX-1- and 2-dependent pathways.

KEYWORDS Endothelium; Cyclooxygenase; Vasoconstricting factor(s); Remodeling; Prostanoids


Time for primary review: 25 days


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